126
8
conhydrine and N-methylconiine. They are found in plants such as poison hemlock
(Conium maculatum), and the equivalent to about six to eight fresh leaves or an even
smaller dose of seeds or root is deadly. It is most famously known for the death of Greek
philosopher Socrates 399 BC (Dayan 2009), and it was also suggested by recent research
that Cleopatra might have chosen a mixture of hemlock, wolfsbane and opium to kill
herself (Mebs and Schäfer 2008). So, while already a well-known poison in ancient
times, it was still a preferred toxin of choice in medieval times at least in literature. For
example, Shakespeare referred to hemlock in The Life of Henry the Fifth and Macbeth.
There has been some use as external medication; however, the high toxicity of the plant
has favoured its use as a poison (Vetter 2004). Coniine is also found in the nectar of the
yellow pitcher plant, Sarracenia flava, and it was suggested that the plants use it to stun
trapped insects. If so, it would make the yellow pitcher plants especially devious since it
attracts insects with its nectar and pollen, then poisons and finally eats them (Mody
et al. 1976).
Methyllycaconitine is a diterpene alkaloid from Delphinium (larkspur), perennial
plants that are found throughout the Northern Hemisphere. It is toxic to mammals and
has been the cause of livestock poisoning in North America. However, its use as an
insecticide was already described by Plinus, the Elder (Jennings et al. 1986). It was
shown to be especially toxic for insect due to its high affinity for the insect nicotinic
acetylcholine receptor indicating that insectoid herbivores might be the primary target
of the compound.
Plant- and insect-derived alkaloids that target the nicotinic acetylcholine receptor
(and other ligand-activated channels) also have long been used by tribal hunters in South
and Middle America to poison their arrows and darts. The term curare is used for arrow
toxins based on different mixtures of plant extracts. In 1895, Rudolf Boehm, a German
pharmacist, classified three variants of curare (Boehm 1897). Bamboo or tube curare
contains d-tubocurarine, a benzylisoquinoline alkaloid, as the major active ingredient.
The plant extracts are mostly made from bark of the South American climbing plant
Chondrodendron tomentosum (King 1948), but the active ingredient is also found in
other plants from the genus Chondrodendron as well as plants from the closely related
genera Curarea, Caryomene, Cissampelos and Strychnos such as Strychnos toxifera
(Philippe et al. 2004). Pot curare contains mainly protocurarine, protocurine and protocuridine, while the major active ingredient of calabash curare is C-curarine I (Battersby
and Hodson 1965).
During their travels into the “New World”, German scientist Alexander von Humbold
and his French college Aimé Bonpland were the first Europeans that were shown the
Box 8.2 Defensive halitosis
Several insects have learned to use plant-derived secondary metabolites for their own
defences. Caterpillars of the tobacco hornworm transport part of the nicotine taken up by
chewing on tobacco leaves or its non-toxic derivatives from the midgut to the haemolymph.
From there, nicotine is released into the air through spiracles in their flanks to ward of predators such as the native wolf spider. These caterpillars get eaten when they are fed on nicotinedeficient mutant tobacco (Kumar et al. 2014). However, this defence system seems to come
with a cost. Worms feeding on nicotine-deficient tobacco grow bigger and faster than those
feeding on plants with normal nicotine levels, indicating that the worms are still partially
affected by the drug
Chapter 8 · Plant-Derived Drugs Affecting Ion Channels
8
conhydrine and N-methylconiine. They are found in plants such as poison hemlock
(Conium maculatum), and the equivalent to about six to eight fresh leaves or an even
smaller dose of seeds or root is deadly. It is most famously known for the death of Greek
philosopher Socrates 399 BC (Dayan 2009), and it was also suggested by recent research
that Cleopatra might have chosen a mixture of hemlock, wolfsbane and opium to kill
herself (Mebs and Schäfer 2008). So, while already a well-known poison in ancient
times, it was still a preferred toxin of choice in medieval times at least in literature. For
example, Shakespeare referred to hemlock in The Life of Henry the Fifth and Macbeth.
There has been some use as external medication; however, the high toxicity of the plant
has favoured its use as a poison (Vetter 2004). Coniine is also found in the nectar of the
yellow pitcher plant, Sarracenia flava, and it was suggested that the plants use it to stun
trapped insects. If so, it would make the yellow pitcher plants especially devious since it
attracts insects with its nectar and pollen, then poisons and finally eats them (Mody
et al. 1976).
Methyllycaconitine is a diterpene alkaloid from Delphinium (larkspur), perennial
plants that are found throughout the Northern Hemisphere. It is toxic to mammals and
has been the cause of livestock poisoning in North America. However, its use as an
insecticide was already described by Plinus, the Elder (Jennings et al. 1986). It was
shown to be especially toxic for insect due to its high affinity for the insect nicotinic
acetylcholine receptor indicating that insectoid herbivores might be the primary target
of the compound.
Plant- and insect-derived alkaloids that target the nicotinic acetylcholine receptor
(and other ligand-activated channels) also have long been used by tribal hunters in South
and Middle America to poison their arrows and darts. The term curare is used for arrow
toxins based on different mixtures of plant extracts. In 1895, Rudolf Boehm, a German
pharmacist, classified three variants of curare (Boehm 1897). Bamboo or tube curare
contains d-tubocurarine, a benzylisoquinoline alkaloid, as the major active ingredient.
The plant extracts are mostly made from bark of the South American climbing plant
Chondrodendron tomentosum (King 1948), but the active ingredient is also found in
other plants from the genus Chondrodendron as well as plants from the closely related
genera Curarea, Caryomene, Cissampelos and Strychnos such as Strychnos toxifera
(Philippe et al. 2004). Pot curare contains mainly protocurarine, protocurine and protocuridine, while the major active ingredient of calabash curare is C-curarine I (Battersby
and Hodson 1965).
During their travels into the “New World”, German scientist Alexander von Humbold
and his French college Aimé Bonpland were the first Europeans that were shown the
Box 8.2 Defensive halitosis
Several insects have learned to use plant-derived secondary metabolites for their own
defences. Caterpillars of the tobacco hornworm transport part of the nicotine taken up by
chewing on tobacco leaves or its non-toxic derivatives from the midgut to the haemolymph.
From there, nicotine is released into the air through spiracles in their flanks to ward of predators such as the native wolf spider. These caterpillars get eaten when they are fed on nicotinedeficient mutant tobacco (Kumar et al. 2014). However, this defence system seems to come
with a cost. Worms feeding on nicotine-deficient tobacco grow bigger and faster than those
feeding on plants with normal nicotine levels, indicating that the worms are still partially
affected by the drug
Chapter 8 · Plant-Derived Drugs Affecting Ion Channels